Benzaldehydes anti-aldol formation

When an enolate is forced to take the E configuration, e.g, the enolate derived from cyclohexanone, predominant formation of the anti-aldol might be expected. Surprisingly, early experiments gave more or less stereorandom results in that the reaction with benzaldehyde gave a ratio of. vvtt/ant/ -aldols of 48 521B 23, Contrarily, recent investigations24 reveal a substantial anti selectivity (16 84), which is lowered in a dramatic manner (50 50) by the presence of lithium salts. Thus, the low stereoselectivity in the early experiments may be attributed to impurities of lithium salts or lithium hydroxide. 

The aldol reaction of 2,2-dimethyl-3-pentanone, which is mediated by chiral lithium amide bases, is another route for the formation of nonracemic aldols. Indeed, (lS,2S)-l-hydroxy-2,4,4-trimethyl-l-phenyl-3-pentanone (21) is obtained in 68% ee, if the chiral lithiated amide (/ )-A-isopropyl-n-lithio-2-methoxy-l-phenylethanamine is used in order to chelate the (Z)-lithium cnolate, and which thus promotes the addition to benzaldehyde in an enantioselective manner. No anti-adduct is formed25. 

When TiCU is used as a catalyst with substituted dienes such as (14), a predominant route is the Mu-kaiyama aldol process, " When diene (14) reacts with benzaldehyde the trans (anti) product is observed. When compound (42) is used as the aldehyde, one observes exclusive formation of the (erythro) aldol products (Table 14). These stereochemical results can be rationalized by using a Zimmerman-Traxler transition state (Scheme 18). Chelation by the metal of the aldehyde a-alkoxy group causes it to be placed in a pseudo axial position in the transition state structure. This results in a stereochemical relationship that gives syn aldol products. ... 

Planar chiral ortho substituted benzaldehyde chromium complexes are useful compounds for a variety of asymmetric reactions. For example, planar chiral tricarbonylchromium complexes of o-substituted benzaldehydes were reacted with Danishefsky s diene in the presence of Lewis acid at room temperature to afford the chromium-complexed 2,3-dihydro-4-pyranones 25 with high dias-tereoselectivity (Eq. 15) [14]. The high diastereoselectivity of the formation of cycloaddition products 25 is also contributed to an exo-side approach of the diene to anti-oriented carbonyl oxygen of the planar chiral ortho substituted benzaldehyde chromium complexes. When the reaction takes place at lower temperature, aldol-type condensation product 26 was obtained along with the formation of pyranones. The open intermediate 26 was easily transformed to the corresponding cycloaddition product after stirring at room temperature [14]. 

The enantioselective intermolecular reductive aldol reaction with enone instead of ester is also an important C-C bond formation reaction. The coupling reaction of cyclopent-2-enone and benzaldehyde with hydrosilane in the presence of 1 mol% of the phebox-Rh complex 5-Ph smoothly proceeded to give the corresponding anti-p-hydroxyketone 29 with the high ee value (Scheme 20) [25], On the basis of the absolute configuration of 29, the transition state of the reaction might involve the Re face attack of the Rh enolate to the Re face of the aldehyde captured on the rhodium atom leading to form 2S, l R-diastereomeric product. 

Stereoselectivities of aldol reactions of trimethoxysilyl enol ethers catalysed by lithium binaphthoate are greatly affected by the presence of water, which may induce a change from anti- to iyn-adduct formation for those derived from cyclohexanone, for example. " Direct anti- and regio-specific aldol reactions of cyclododecanone with 0 benzaldehyde in NaOH/MeOH have provided building blocks for helical construction of supramolecules. ... 

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